ArticleThe Journal of biological chemistry2009
A highly conserved motif within the NH2-terminal coiled-coil domain of angiopoietin-like protein 4 confers its inhibitory effects on lipoprotein lipase by disrupting the enzyme dimerization.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 116 citations in OpenAlex.
- MAnimals : an open access journal from MDPI · 2026Article
- Angiopoietin-like 3 monomers are abundant in human plasma but are unable to inhibit endothelial lipase.JCI insight · 2025Article
- ANGPTL3 and residual atherosclerotic risk: from lipid metabolism to therapeutic targeting.Frontiers in endocrinology · 2025Review
- Exercise-Induced cytokines, diet, and inflammation and their role in adipose tissue metabolism.Health science reports · 2024Review
- Angiopoietin-like 4 protects against endothelial dysfunction during bacterial sepsis.Nature microbiology · 2024Article
- Proanthocyanidins and Phenolic Compounds from the Twigs ofNutrients · 2024Article
- Endothelial lipase variant T111I does not alter inhibition by angiopoietin-like proteins.Scientific reports · 2024Article
- Macromolecular Interactions of Lipoprotein Lipase (LPL).Sub-cellular biochemistry · 2024Review
- A nomogram based on the expression level of angiopoietin-like 4 to predict the severity of community-acquired pneumonia.BMC infectious diseases · 2023Article
- Genome-Wide Association Study of Maternal Genetic Effects on Intramuscular Fat and Fatty Acid Composition in Rabbits.Animals : an open access journal from MDPI · 2023Article
- Genetic Mimicry Analysis Reveals the Specific Lipases Targeted by the ANGPTL3-ANGPTL8 Complex and ANGPTL4.Journal of lipid research · 2023Article
- Biochemical, Clinical, and Genetic Characteristics of Mexican Patients with Primary Hypertriglyceridemia, Including the First Case of Hyperchylomicronemia Syndrome Due to GPIHBP1 Deficiency.International journal of molecular sciences · 2022Article
- An anti-ANGPTL3/8 antibody decreases circulating triglycerides by binding to a LPL-inhibitory leucine zipper-like motif.Journal of lipid research · 2022Article
- Causes, clinical findings and therapeutic options in chylomicronemia syndrome, a special form of hypertriglyceridemia.Lipids in health and disease · 2022Review
- An updated ANGPTL3-4-8 model as a mechanism of triglyceride partitioning between fat and oxidative tissues.Progress in lipid research · 2022Review
- Regulation of lipoprotein metabolism by ANGPTL3, ANGPTL4, and ANGPTL8.American journal of physiology. Endocrinology and metabolism · 2021Review
- Single nucleotide polymorphisms in the ANGPTL4 gene and the SNP-SNP interactions on the risk of atherosclerotic Ischaemic stroke.BMC neurology · 2021Article
- ANGPLT3 in cardio-metabolic disorders.Molecular biology reports · 2021Review
- Apolipoprotein CIII and Angiopoietin-like Protein 8 are Elevated in Lipodystrophy and Decrease after Metreleptin.Journal of the Endocrine Society · 2021Article
- GPIHBP1 and ANGPTL4 Utilize Protein Disorder to Orchestrate Order in Plasma Triglyceride Metabolism and Regulate Compartmentalization of LPL Activity.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipoprotein lipase (LPL) is a principal enzyme responsible for the clearance of chylomicrons and very low density lipoproteins from the bloodstream. Two members of the Angptl (angiopoietin-like protein) family, namely Angptl3 and Angptl4, have been shown to inhibit LPL activity in vitro and in vivo. Here, we further investigated the structural basis underlying the LPL inhibition by Angptl3 and Angptl4. By multiple sequence alignment analysis, we have identified a highly conserved 12-amino acid consensus motif that is present within the coiled-coil domain (CCD) of both Angptl3 and Angptl4, but not other members of the Angptl family. Substitution of the three polar amino acid residues (His(46), Gln(50), and Gln(53)) within this motif with alanine abolishes the inhibitory effect of Angptl4 on LPL in vitro and also abrogates the ability of Angptl4 to elevate plasma triglyceride levels in mice. The CCD of Angptl4 interacts with LPL and converts the catalytically active dimers of LPL to its inactive monomers, whereas the mutant protein with the three polar amino acids being replaced by alanine loses such a property. Furthermore, a synthetic peptide consisting of the 12-amino acid consensus motif is sufficient to inhibit LPL activity, although the potency is much lower than the recombinant CCD of Angptl4. In summary, our data suggest that the 12-amino acid consensus motif within the CCD of Angptl4, especially the three polar residues within this motif, is responsible for its interaction with and inhibition of LPL by blocking the enzyme dimerization.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.